Heat stress implies unfavorable effects on primary and functional traits in dairy cattle and, in consequence, on the profitability of the whole production system. The increasing number of days with extreme hot temperatures suggests that it is imperative to detect the heat stress status of animals based on adequate measures. However, confirming the heat stress status of an individual is still challenging, and, in consequence, the identification of novel heat stress biomarkers, including molecular biomarkers, remains a very relevant issue. Currently, it is known that heat stress seems to have unfavorable effects on immune system mechanisms, but this information is of limited use in the context of heat stress phenotyping. In addition, there is a lack of knowledge addressing the molecular mechanisms linking the relevant genes to the observed phenotype. In this review, we explored the potential molecular mechanisms explaining how heat stress affects the immune system and, therefore, increases the occurrence of immune-related diseases in cattle. In this regard, 2 relatively opposite hypotheses are under focus: the immunosuppressive action of cortisol, and the proinflammatory effect of heat stress. In both hypotheses, the modulation of the immune response during heat stress is highlighted. Moreover, it is possible to link candidate genes to these potential mechanisms. In this context, immune markers are very valuable indicators for the detection of heat stress in dairy cattle, broadening the portfolio of potential biomarkers for heat stress.

This genome-wide association study (GWAS) aimed to identify sequence variants (SVs) and candidate genes associated with fertility and health in endangered German Black Pied cattle (DSN) based on whole-genome sequence (WGS) data. We used 304 sequenced DSN cattle for the imputation of 1797 genotyped DSN to WGS. The final dataset included 11,413,456 SVs of 1886 cows. Cow traits were calving-to-first service interval (CTFS), non-return after 56 days (NR56), somatic cell score (SCS), fat-to-protein ratio (FPR), and three pre-corrected endoparasite infection traits. We identified 40 SVs above the genome-wide significance and suggestive threshold associated with CTFS and NR56, and three important potential candidate genes (ARHGAP21, MARCH11, and ZNF462). For SCS, most associations were observed on BTA 25. The GWAS revealed 61 SVs, a cluster of 10 candidate genes on BTA 13, and 7 pathways for FPR, including key mediators involved in milk fat synthesis. The strongest associations for gastrointestinal nematode and Dictyocaulus viviparus infections were detected on BTA 8 and 24, respectively. For Fasciola hepatica infections, the strongest associated SVs were located on BTA 4 and 7. We detected 200 genes for endoparasite infection traits, related to 16 pathways involved in host immune response during infection.

Gastrointestinal nematodes (GIN), liver flukes (Fasciola hepatica) and bovine lungworms (Dictyocaulus viviparus) are the most important parasitic agents in pastured dairy cattle. Endoparasite infections are associated with reduced milk production and detrimental impacts on female fertility, contributing to economic losses in affected farms. In quantitative-genetic studies, the heritabilities for GIN and F. hepatica were moderate, encouraging studies on genomic scales. Genome-wide association studies (GWAS) based on dense single nucleotide polymorphism (SNP) marker panels allow exploration of the underlying genomic architecture of complex disease traits. The current GWAS combined the identification of potential candidate genes with pathway analyses to obtain deeper insights into bovine immune response and the mechanisms of resistance against endoparasite infections. A 2-step approach was applied to infer genome-wide associations in an endangered dual-purpose cattle subpopulation [Deutsches Schwarzbuntes Niederungsrind (DSN)] with a limited number of phenotypic records. First, endoparasite traits from a population of 1166 Black and White dairy cows [including Holstein Friesian (HF) and DSN] naturally infected with GIN, F. hepatica and D. viviparus were precorrected for fixed effects using linear mixed models. Afterwards, the precorrected phenotypes were the dependent traits (rFEC-GIN, rFEC-FH, and rFLC-DV) in GWAS based on 423,654 SNPs from 148 DSN cows. We identified 44 SNPs above the genome-wide significance threshold (pBonf = 4.47 × 10− 7), and 145 associations surpassed the chromosome-wide significance threshold (range: 7.47 × 10− 6 on BTA 1 to 2.18 × 10− 5 on BTA 28). The associated SNPs identified were annotated to 23 candidate genes. The DAVID analysis inferred four pathways as being related to immune response mechanisms or involved in host-parasite interactions. SNP effect correlations considering specific chromosome segments indicate that breeding for resistance to GIN or F. hepatica as measured by fecal egg counts is genetically associated with a higher risk for udder infections. We detected a large number of loci with small to moderate effects for endoparasite resistance. The potential candidate genes regulating resistance identified were pathogen-specific. Genetic antagonistic associations between disease resistance and productivity were specific for specific chromosome segments. The 2-step approach was a valid methodological approach to infer genetic mechanisms in an endangered breed with a limited number of phenotypic records.

Background: Nature conservation with reduced drainage of pastures has been increasingly promoted in agriculture in recent years. However, moisture on pastures is a crucial factor for the development of free-living stages of many parasite species in ruminants. Hence, for the first time, we conducted a field study between 2015 and 2017 at the German North Sea coast to investigate the long-term effect of pasture rewetting (since 2004) on endoparasite infections in sheep and cattle. Methods: We examined faecal samples of 474 sheep and 646 cattle from five farms in spring, summer and autumn each year for the presence of endoparasite infections. Animals were kept on conventionally drained, undrained and rewetted pastures. The association between pasture rewetting and endoparasite infection probability was analysed in generalized linear mixed models and including further potential confounders. Results: Infection frequencies for gastrointestinal strongyles, Eimeria spp. and Strongyloides papillosus were significantly higher in sheep (62.9%, 31.7% and 16.7%) than in cattle (39.0%, 19.7% and 2.6%). Fasciola hepatica was detected with a frequency of 13.3% in sheep and 9.8% in cattle, while rumen fluke frequency was significantly higher in cattle (12.7%) than in sheep (3.8%). Nematodirus spp., lungworms (protostrongylids, Dictyocaulus viviparus), Moniezia spp., Trichuris spp. and Dicrocoelium dendriticum were identified in less than 7% of samples. Co-infection with more than three endoparasite taxa was present significantly more often in sheep than in cattle. We identified significant positive correlations above 0.2 for excretion intensities between S. papillosus with strongyles, Eimeria spp. and Nematodirus spp. in sheep and between strongyles and Nematodirus spp. in cattle. Pasture rewetting had no long-term effect on endoparasite infections, neither in sheep nor in cattle. Interestingly, F. hepatica infections decreased significantly in sheep and cattle from 2015 (10.9% and 13.9%) to 2017 (1.4% and 2.1%). Conclusions: Pasture rewetting for nature conservation did not increase endoparasite infection probability in ruminants in the long term. This finding should be confirmed in ongoing studies aimed at further animal welfare parameters. The rapid decrease in F. hepatica infections over 3 years may suggest climatic impact or competition with rumen flukes in addition to potential anthelmintic treatment after feedback of the results to the farmers. Graphical

German Black Pied (DSN) is considered an ancestral population of the Holstein breed. The goal of the current study was to fine-map genomic loci for milk production traits and to provide sequence variants for selection. We studied genome-wide associations for milk-production traits in 2160 DSN cows. Using 11.7 million variants from whole-genome sequencing of 304 representative DSN cattle, we identified 1980 associated variants (−log₁₀(p) ≥ 7.1) in 13 genomic loci on 9 chromosomes. The highest significance was found for the MGST1 region affecting milk fat content (−log₁₀(p) = 11.93, MAF = 0.23, substitution effect of the minor allele (ß_MA) = −0.151%). Different from Holstein, DGAT1 was fixed (0.97) for the alanine protein variant for high milk and protein yield. A key gene affecting protein content was CSN1S1 (−log₁₀(p) = 8.47, MAF = 049, ß_MA = −0.055%) and the GNG2 region (−log₁₀(p) = 10.48, MAF = 0.34, ß_MA = 0.054%). Additionally, we suggest the importance of FGF12 for protein and fat yield, HTR3C for milk yield, TLE4 for milk and protein yield, and TNKS for milk and fat yield. Selection for favored alleles can improve milk yield and composition. With respect to maintaining the dual-purpose type of DSN, unfavored linkage to genes affecting muscularity has to be investigated carefully, before the milk-associated variants can be applied for selection in the small population.