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The present study was conducted to examine differential expression pattern of HSP genes and adaptability in Indian goat breeds of semi-arid region. The study was conducted in five animals from each breed viz. Barbari, Sirohi, and Jhakrana during winter, thermo-neutral and summer seasons. The respiratory rate (RR) and rectal temperature (RT) of the goats were recorded at 09: 00 h during the study period. The blood samples were collected for RNA isolation, cDNA synthesis, and quantitative analysis of HSP genes expression by quantitative RT-PCR. The RR increased significantly (p < 0.01) during summer as compared to winter and thermo-neutral season however, RT did not change (p > 0.05) during different seasons. The expression of HSP genes was significantly (p < 0.01) increased during summer (high THI) as compared to thermo-neutral season in all the goat breeds. Among HSPs, only HSP90 was upregulated (p < 0.01) in Jhakrana goats during winter as compared to thermo-neutral season. The deviation in expression of HSP genes during summer and winter with respect to thermo-neutral season was minimum in Barbari goats. Therefore, it can be concluded that Barbari goats possessed better adaptability during summer and winter as compared to Sirohi and Jhakrana goats in semi-arid climatic conditions of India.