Multi-Omics Analysis Reveals New Insights into Yak Lung Under High-Altitude Adaptation

The yak lung functions as a vital adaptive organ in cold, low-oxygen environments. Hypoxia can induce pathological remodeling in yak lung tissue, so we need to understand the molecular mechanisms of this remodeling. For this study, we used cross-omics comparative approaches, including transcriptomics, label-free proteomics, and untargeted metabolomics, to examine both normal and diseased yak lung tissues. From histological observations, the disease phenotype was identified as pulmonary emphysema. Our results showed a significant up-regulation of differentially expressed genes such as MTTP, CXCL8, RETN, and NNAT, while genes like SLC45A1, IL10, SDSL, and COL12A1 were clearly down-regulated. In the differential protein analysis, proteins such as RASSF4, EDC4, CTSC, and FECH were notably up-regulated, whereas CYP27A1, FKBP9, RAD23A, and PLSCR2 were significantly down-regulated. Metabolomic profiling revealed that palmitoyl-L-carnitine, decanoyl-L-carnitine, and o-acetylcarnitine were significantly higher in emphysematous lung tissue, whereas racemethionine and L-methionine S-oxide were significantly much lower. Also, when we compared of bulk RNA-seq, label-free proteomics, and untargeted metabolomics data revealed enrichment in three common pathways: the asthma pathway, the linoleic acid metabolism pathway, and the gastric acid secretion pathway. Of note, histamine levels were higher in both the asthma and gastric acid secretion pathways. While the mRNA expression level of BoLA-DQB was increased in the asthma pathway, its protein expression level was decreased. This study offers some initial cross-omics evidence about what happens. These findings give us a scientific basis for developing effective prevention and control strategies, which in turn can help the protection of yak health and the sustainable development of plateau animal husbandry.