Exposure to high ambient temperature has detrimental effects on poultry welfare and production. Although changes in gene expression due to heat exposure have been well described for broiler chickens, knowledge of the effects of heat on laying hens is still relatively limited. In this study, we profiled the transcriptome for pectoralis major muscle (n = 24) and liver (n = 24), during a 4-week cyclic heating experiment performed on layers in the early phase of egg production. Both heat-control and time-based contrasts were analyzed to determine differentially expressed genes (DEGs). Heat exposure induced different changes in gene expression for the two tissues, and we also observed changes in gene expression over time in the control animals suggesting that metabolic changes occurred during the transition from onset of lay to peak egg production. A total of 73 DEGs in liver were shared between the 3 h heat-control contrast, and the 4-week versus 3 h time contrast in the control group, suggesting a core set of genes that is responsible for maintenance of metabolic homeostasis regardless of the physiologic stressor (heat or commencing egg production). The identified DEGs improve our understanding of the layer’s response to stressors and may serve as targets for genetic selection in the future to improve resilience.