Abstract
<title>Abstract</title> <p>Heat stress is a major limitation to beef cattle production, particularly in subtropical and tropical regions where rising temperatures can negatively impact animal performance and health. This study investigated the molecular mechanisms underlying thermotolerance in Brangus beef cattle using integrated phenotypic and transcriptomic approaches. Cattle were classified as thermotolerant or non-thermotolerant based on core body temperature responses to changes in temperature-humidity index. Blood samples were collected under two distinct environmental conditions, and RNA sequencing was performed to evaluate differential gene expression. The repeated-measures experimental design revealed distinct transcriptional patterns between groups: thermotolerant animals exhibited more stable expression profiles, whereas non-thermotolerant animals displayed broader transcriptional changes, suggesting different molecular strategies for coping with environmental variation and heat stress. This study identified candidate genes associated with thermotolerance, offering insights into key biological pathways that could be targeted to improve heat resilience in cattle. The identified candidate genes offer valuable potential for genetic selection programs aimed at improving the productivity of beef cattle operations, helping to address challenges posed by global climate change and the increasing need for resilient livestock.</p>