Chronic heat stress induces hepatic injury, alters hematological parameters, thermotolerance response in gilts through liver multi-omics analysis.

Global climate warming elevates temperatures, increasing pigs' heat stress susceptibility and metabolic heat production, thereby intensifying heat-related challenges. This study examines chronic heat stress (HS) effects on hematological traits and hepatic responses in gilts. During HS, respiratory rate and surface temperature rose significantly, while rectal temperature stabilized. In the HS group, white blood cell count, aonocyte percentage, eosinophil percentage, absolute eosinophil count, absolute neutrophil count, absolute monocyte count, absolute basophil count, hematocrit, and mean corpuscular hemoglobin concentration decreased markedly, whereas mean platelet volume increased. Blood Beecf and PO2 levels rose, and PCO2 levels dropped. HS elevated cortisol, altered thyroid function (higher TSH, lower T3/T4), reduced ACTH indicating adrenal dysfunction, and disrupted reproductive hormones (higher LH, lower FSH) alongside elevated insulin (INS) and estradiol (E2) levels. Furthermore, Albumin/Globulin Ratio (A/G ratio) and Albumin (ALB) decreased, while Alkaline Phosphatase (ALP), Gamma-Glutamyl Transferase (GGT), Globulin (GLB), Total Bile Acids (TBA), and Total Bilirubin (TBIL) increased. Histopathology revealed hepatic punctate necrosis, lymphocyte infiltration, sinusoidal dilation, and hydropic degeneration. Immunofluorescence showed increased Bax+ and CD3+ cells but decreased Bcl-2+ and CD3+ cells. Hepatocyte HSP70/90 levels surged. Multi-omics analysis indicated HS enriched oxidative phosphorylation, steroid biosynthesis, lipid metabolism, and thyroid hormone synthesis in the liver. Pro-inflammatory pathways (Calcitriol, LPC 19:0) were activated, while protective molecules (Cholecalciferol, L-Glutathione) countered oxidative stress. As expected, chronic HS impairs liver function, induces an inflammation-antioxidant imbalance. More importantly, HS accelerates the conversion of cholesterol to sex hormones to compensate for ovarian suppression, ultimately affecting gilt reproductive performance.