Elevated environments such as plateaus are often classified as low oxygen environments. The hypoxic adaptation mechanisms utilized by organisms in these conditions are not well understood. To address this, the differentially expressed genes (DEGs) involved in hypoxia adaptation were assessed using two pig breeds (Tibetan pig [TP] and Yorkshire sow [YY]). Genes related to lung tissue responses to hypoxia were assessed using transcriptomic (using RNA-seq) and proteomic (using iTRAQ) analysis. A total of 1021 DEGs were screened out. In the iTRAQ omics data, a total of 22,100 peptides were obtained and 4518 proteins were found after filtering. A total of 271 differentially expressed proteins [DEPs] were screened using the conditions of p < 0.05; FC ≤ 0.833; and FC ≥ 1.2. A total of 14 DEGs at the mRNA and protein levels were identified and found to be associated with regulation of the inflammatory response; blood particles; and MAPK cascade response regulation. Among the DEGs, six were associated with hypoxia adaptation function (mitochondria and glycolysis) in pigs. The results of this study identify novel candidate genes involved in porcine hypoxia adaptation mechanisms.