In meat-producing animals, preslaughter operations ( e.g ., transportation, mixing unfamiliar animals, food and water deprivation) may be a source of stress with detrimental effects on meat quality. The objective of this work was to study the effect of emotional and physical stress by comparing the transcriptomes of two muscles (M. longissimus thoracis, LT and M. semitendinosus, ST ) in Normand cows exposed to stress ( n = 16) vs . cows handled with limited stress ( n = 16). Using a microarray, we showed that exposure to stress resulted in differentially expressed genes (DEGs) in both muscles (62 DEGs in LT and 32 DEGs in ST, of which eight were common transcription factors (TFs)). Promoter analysis of the DEGs showed that 25 cis transcriptional modules were overrepresented, of which nine were detected in both muscles. Molecular interaction networks of the DEGs targeted by the most represented cis modules helped identify common regulators and common targets involved in the response to stress. They provided elements showing that the transcriptional response to stress is likely to (i) be controlled by regulators of energy metabolism, factors involved in the response to hypoxia, and inflammatory cytokines; and (ii) initiate metabolic processes, angiogenesis, corticosteroid response, immune system processes, and satellite cell activation/quiescence. The results of this study demonstrate that exposure to stress induced a core response to stress in both muscles, including changes in the expression of TFs. These factors could relay the physiological adaptive response of cattle muscles to cope with emotional and physical stress. The study provides information to further understand the consequences of these molecular processes on meat quality and find strategies to attenuate them.