Porcine reproductive and respiratory syndrome virus (PRRSV) is a single-stranded positive-sense RNA virus that can cause devastating reproductive failure and respiratory tract lesions, which has led to serious damage to the swine industry worldwide. Our previous studies have indicated that Tongcheng (TC) pigs, a Chinese local breed, have stronger resistance or tolerance to PRRSV infection than Large White (LW) pigs. This study aims to investigate their host transcriptome differences in porcine alveolar macrophages (PAMs) at 7 days post challenge. Transcriptome profiling of PAMs from PRRSV infected and control pigs of these two breeds were performed using RNA-sequencing. For both breeds, there were 1257 common differentially expressed genes (DEGs) in response to PRRSV infection, involving hepatic fibrosis/hepatic stellate cell activation, phospholipase C, and granulocyte adhesion and diapedesis pathways. For TC pig, 549 specific DEGs were identified, including VAV2, BCL2 and BAX, which were enriched in activation of leukocyte extravasation and suppression of apoptosis. While, 898 specific DEGs were identified in LW pigs, including GNAQ, GNB5, GNG2, CALM4 and RHOQ, which were involved in suppression of Gαq and PI3K-AKT signaling. This study provides an insight into the transcriptomic comparison of resistant and susceptible pigs to PRRSV infection. TC pigs may promote the extravasation and migration of leukocytes to defend against PRRSV infections and suppress apoptosis of the infected macrophages to increase antigen presentation, thereby reducing the lung lesions.

Alternative splicing (AS) plays a significant role in regulating gene expression at the transcriptional level in eukaryotes. Flexibility and diversity of transcriptome and proteome can be significantly increased through alternative splicing of genes. In the present study, transcriptome data of peripheral immune organs including spleen and inguinal lymph nodes (ILN) were used to identify AS difference between PRRSV‐resistant Tongcheng (TC) pigs and PRRSV‐susceptible Large White (LW) pigs artificially infected with porcine reproductive and respiratory syndrome virus (PRRSV) in vivo. The results showed that PRRSV infection induced global alternative splicing events (ASEs) with different modes. Among them, 373 genes and 595 genes in the spleen and ILN of TC pigs, while 458 genes and 560 genes in the spleen and ILN of LW pigs had significantly differential ASEs. Alternative splicing was subject to tissue‐specific and lineage‐specific regulation in response to PRRSV infection. Enriched GO terms and pathways showed that genes with differential ASEs played important roles in transcriptional regulation, immune response, metabolism, and apoptosis. Furthermore, a splicing factor associated with apoptosis, SRSF4, was significantly upregulated in LW pigs. Functional analysis on apoptosis associated genes was validated by RT‐PCR and DNA sequencing. These findings revealed different response to PRRSV between PRRSV‐resistant TC pigs and PRRSV‐susceptible LW pigs at the level of alternative splicing, suggesting the potential relationship between AS and disease resistance to PRRSV.