New insights into host adaptation to swine respiratory disease revealed by genetic differentiation and RNA sequencing analyses.

Swine respiratory disease (SRD) causes massive economic losses in the swine industry and is difficult to control and eradicate on pig farms. Here, we employed population genetics and transcriptomics approaches to decipher the molecular mechanism of host adaptation to swine respiratory disease. We recorded two SRD-related traits, the enzootic pneumonia-like (EPL) score and lung lesion (LL) levels, and performed four body weight measurements, at ages of 150, 180, 240, and 300 days, in a Chinese Bamaxiang pig herd ( = 314) raised under consistent indoor rearing conditions. We divided these animals into disease-resistant and disease-susceptible groups based on the most likely effects of both SRD-related traits on their weight gain, and performed genetic differentiation analyses in these two groups. Significant loci showing the top 1% of genetic differentiation values, exceeding the threshold of  = 0.005 set based on 1,000-times permutation tests, were defined as candidate regions related to host resistance or susceptibility to SRD. We identified 107 candidate genes within these regions, which are mainly involved in the biological processes of immune response, fatty acid metabolism, lipid metabolism, and growth factor signaling pathways. Among these candidate genes, , , , , and were highlighted due to their central regulatory roles in host immune response or fat metabolism and their differential expression between healthy lung tissues and lung lesions. These findings advance our understanding of the molecular mechanisms of host resistance or susceptibility to respiratory disease in pigs and are of significance for the breeding pigs resistant to respiratory disease in the swine industry.