Nasif I Abbas, Ahmed A Al-Haidary, Ibrahim A Alhidary, Hani H Al-Baadani, Emad M Samara, Mohammed A Al-Badwi, Khalid A Abdoun, Isiaka O Olarinre, Abdulrahman S Alharthi
Climate change is an increasing threat to livestock production in arid regions. Understanding how indigenous breeds deploy immediate acute physiological and biochemical adjustments to acute hyperthermia at systemic and transcript-level indices is necessary to isolate initial homeostatic limits. This research compared the short-term thermoregulatory, metabolic, and multi-tissue transcriptomic adjustments of Naemi and Harri lambs exposed to acute heat stress. Forty male lambs (Naemi, Harri) were subjected to a 180-min exposure to either thermoneutral (25.0 °C Ta, 38.0% RH) or severe acute heat-stress (50.0 °C Ta, 13.2% RH) conditions in a controlled environmental chamber using a repeated-measures mixed-model approach. Thermophysiological kinetics, serum biochemistry, and relative mRNA expression of protective and metabolic genes (HSP70, HSP90, PKM2, SCARB1, FGA) in hepatic, skeletal muscle, and adipose tissues were evaluated after exposure. Acute heat stress induced a severe hyperthermic challenge without animal mortality. Harri lambs prioritized homeothermic defense through an intense, energy-demanding respiratory cooling response (panting). This active effort was accompanied by increased circulating glucose, triglycerides, and β-hydroxybutyrate, along with a concurrent increase in hepatic and muscle SCARB1 transcript abundance. In contrast, Naemi lambs showed a distinct homeostatic buffering response through transient heterothermy and elevated baseline mRNA expression levels of the heat shock protein HSP90 in hepatic tissue and HSP70 in muscle tissue. Additionally, Naemi lambs showed a substantial, tissue-specific increase in FGA transcripts in subcutaneous adipose tissue, reflecting a localized transcriptional response within the fat tail matrix. These findings provide an integrated view of acute heat-stress coping patterns in two indigenous Saudi sheep breeds and provide exploratory target pathways. Because behavioral patterns, endocrine stress pathways, oxidative stress indicators, and functional protein validations were not performed, these findings represent macro-physiological and transcript-level profiles rather than a comprehensive welfare assessment or definitive functional validation.