Bats have adapted to pathogens through diverse mechanisms, including increased resistance—rapid pathogen elimination, and tolerance—limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology), several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that the elevated basal expression of innate immune genes may lead to increased resistance to infection. Here, we test whether such transcriptional patterns occur in Egyptian fruit bat tissues through single-cell and spatial transcriptomics of gut, lung, and blood cells, comparing gene expression between bat, mouse, and human. Despite numerous recent loss and expansion events of interferons in the bat genome, interferon expression and induction are remarkably similar to that of mouse. In contrast, central complement system genes are highly and uniquely expressed in key regions in bat lung and gut epithelium, unlike in human and mouse. Interestingly, the unique expression of these genes in the bat gut is strongest in the crypt, where developmental expression programs are highly conserved. The complement system genes also evolve rapidly in their coding sequences across the bat lineage. Finally, the bat complement system displays strong hemolytic activity. Together, these results indicate a distinctive transcriptional divergence of the complement system, which may be linked to bat resistance, and highlight the intricate evolutionary landscape of bat immunity.

Hearing loss is a hallmark of aging, typically initially affecting the higher frequencies. In echolocating bats, the ability to discern high frequencies is essential. However, nothing is known about age-related hearing loss in bats, and they are often assumed to be immune to it. We tested the hearing of 47 wild Egyptian fruit bats by recording their auditory brainstem response and cochlear microphonics, and we also assessed the cochlear histology in four of these bats. We used the bats’ DNA methylation profile to evaluate their age and found that bats exhibit age-related hearing loss, with more prominent deterioration at the higher frequencies. The rate of the deterioration was ∼1 dB per year, comparable to the hearing loss observed in humans. Assessing the noise in the fruit bat roost revealed that these bats are exposed to continuous immense noise—mostly of social vocalizations—supporting the assumption that bats might be partially resistant to loud noise. Thus, in contrast to previous assumptions, our results suggest that bats constitute a model animal for the study of age-related hearing loss.

The Egyptian fruit bat displays tolerance to lethal viruses and unique dietary adaptations, but the molecular basis for this is poorly understood. To this end, we generated detailed maps of bat gut, lung and blood cells using spatial and single-cell transcriptomics. We compared bat with mouse and human cells to reveal divergence in genetic programs associated with environmental interactions and immune responses. Complement system genes are transcriptionally divergent, uniquely expressed in bat lung and gut epithelium, and undergo rapid coding-sequence evolution. Specifically in the tip of the gut villus, bat enterocytes express evolutionarily young genes while lacking expression of genes related to specific nutrient absorption. Profiling immune stimulation of PBMCs revealed a monocyte subset with conserved cross-species interferon expression, suggesting strong constraints to avoid an excessive immune response. Our study thus uncovers conserved and divergent immune pathways in bat tissues, providing a unique resource to study bat immunity and evolution.

Urbanisation is a pervasive global phenomenon that exerts strong influence on biodiversity and ecosystems. Many species can thrive in urban landscapes by capitalising on generalist traits and environmental resilience; however, this does not safeguard against potential biases exerted by urban environments on population processes. The Egyptian fruit bat ( Rousettus aegyptiacus ) is a species with both urban and rural distribution across its range, and some populations show behavioural and physiological differences. Using reduced representation genome sequencing (ddRAD‐seq), we tested for genetic underpinnings of these differences between urban and rural bat populations sampled across Israel. Despite a genetically homogenous landscape presenting no population structure, we show clear isolation by distance and landscape effects on genetic connectivity, where open areas, but not urbanisation, constitute a barrier to movement. Using genotype‐environment association analysis, we identify 59 candidate SNPs spanning 56 genes potentially associated with urbanisation. This suite of genes entails wide‐ranging functions including neurotransmission, metabolism, gene expression regulation, reproductive biology, and retinoic acid and sensory function. Gene Ontology enrichment analysis revealed non‐random functional clustering with exceptional enrichment in GABAergic synapse components (98.6‐fold), monoatomic ion transport (122.2‐fold), and ATP‐dependent chromatin remodelling (68.6‐fold), evidencing coordinated selection across interconnected neural, metabolic, and regulatory systems. A predominance of intronic variants within this candidate SNP suite (51/59) is suggestive that adaptation in response to urbanisation proceeds primarily through changes in gene regulation, rather than protein‐coding modifications. This study shows how a highly mobile species may undergo microevolutionary shifts in response to urban pressures despite ongoing gene flow, elucidating the complex interplay between genetics and the urban environment in a non‐model organism.