Understanding the potential of coral to adapt to environmental stressors that cause coral bleaching is urgent. The molecular responses of the coral holobiont to such stress conditions determine the success of symbiosis. Therefore, by characterizing molecular stress responses at the holobiont level, we can develop better tools to diagnose its health and resilience. However, only some genomic-scale resources are available for reefbuilding corals from the Eastern Tropical Pacific. This study aimed to perform a transcriptomic characterization of the Pocillopora grandis holobiont following transplantation into environments with different health conditions in Colima, Mexico. Healthy specimens of two color morphotypes (green and brown) were collected in Carrizales, a reef in good condition. Coral fragments from the two morphotypes were relocated within the source location (local transplant stress). In contrast, similar fragments were translocated into another reef with a poorer health state, La Boquita. After 24 h, the transplanted fragments were collected, and RNA-seq was performed with the Illumina system. De novo transcriptome assembly, functional annotation, identification of co-expression modules, and enrichment analysis of molecular pathways were performed. The analysis of rRNA LSU, rRNA SSU, and COI sequences confirmed the coral species, whereas analysis of Rubisco, psbA, and psaA transcripts revealed that the dominant endosymbiont was Durusdinium sp. Gene expression patterns observed across samples suggest that the transplantation to a reef with a poorer state of health affected processes such as photosynthesis, calcium homeostasis, and immune response. The transcriptomic indicators proposed here are valuable for further studies examining the adaptation of Pocillopora corals to global changes.