Distinct Damage Levels and Transcriptional Responses of Lung in Hezuo Pigs and Bama Pigs During Cold Exposure.

[OBJECTIVE] Compare cold adaptation mechanisms between cold-tolerant Hezuo and cold-sensitive Bama pigs.

[METHODS] Lung histology, W/D ratio, oxidative and inflammatory markers, apoptosis, and transcriptomics were analyzed.

[RESULTS] The results showed that the lung of Hezuo pigs displayed less severe alveolar septal thickening, inflammatory infiltration, and fine bronchial fold extension during cold exposure compared to Bama pigs. The W/D ratio dramatically decreased in Hezuo pigs and increased in Bama pigs. Hezuo pigs exhibited significantly higher AQP-1(Aquaporin-1) and AQP-5(Aquaporin-5) expressions than Bama pigs in the middle and late phases. Bama pigs displayed increased ROS(Reactive Oxygen Species), MDA(Malondialdehyde), TNF-α(Tumor Necrosis Factor-alpha), IL-1β(Interleukin-1 beta) and decreased GSH(Glutathione). However, Hezuo pigs maintained stable GSH and showed no significant late-phase inflammatory marker changes. Bama pigs had a higher apoptosis density and number of TUNEL-positive cells than Hezuo pigs, which was related to the down-regulation of Bcl-2(B-Cell Lymphoma 2) and the up-regulation of Bax(BCL2-Associated X Protein) and Caspase-3. Furthermore, Transcriptomic analysis revealed that, in Bama pigs, the distinctive genes-MUC5B(Mucin 5B), MMP9(Matrix Metallopeptidase 9), AMCF-II(Alveolar Macrophage Chemotactic Factor-II), IL22RA1(Interleukin 22 Receptor Subunit Alpha 1), CCL16(C-C Motif Chemokine Ligand 16), SOX9(SRY-Box Transcription Factor 9), KRT5(Keratin 5) function to drive mucus hypersecretion, extracellular matrix degradation, and sustained inflammatory chemotaxis, thereby exacerbating tissue damage. In contrast, the distinctive genes of Hezuo pigs-ALDH1A2(Aldehyde Dehydrogenase 1 Family Member A2), ACSL6(Acyl-CoA Synthetase Long Chain Family Member 6), ACSM5(Acyl-CoA Synthetase Medium Chain Family Member 5), AKR1C1(Aldo-Keto Reductase Family 1 Member C1), NR4A3/2(Nuclear Receptor Subfamily 4 Group A Member 3/2), GNG4(G Protein Subunit Gamma 4), GYS2(Glycogen Synthase 2) primarily enhance lipid metabolism, facilitate aldehyde detoxification, and mitigate oxidative stress, collectively orchestrating a cellular protection mechanism.

[CONCLUSION] Hezuo pigs exhibit protective molecular mechanisms, suggesting candidate targets for cold-resistance breeding.