The guinea pig (Cavia porcellus), a species native to Peru, is valued for its meat production, where muscle development is essential for productive efficiency. The new Kuri breed, obtained through selective breeding and genetic selection, has shown a phenotype with more developed musculature compared to native guinea pigs. In this study, we conducted a comparative transcriptomic analysis between Native and Kuri breed guinea pig, complemented by histological analysis of the semitendinosus muscle to investigate the underlying mechanisms responsible for the differences in muscle morphology. Histological analysis revealed a significant increase in muscle fiber area in the Kuri breed compared to the native guinea pigs. At the molecular level, key mutations were identified in the MSTN gene, including variants in the 3' UTR region and a frameshift mutation, which alter the gene's inhibitory function on muscle growth. Additionally, differences were observed in the expression of pathways related to muscle degradation, energy metabolism, and angiogenesis, which explain the greater muscle hypertrophy in the Kuri breed. These findings provide a first understanding of the genetic mechanisms responsible for muscle hypertrophy in the Kuri breed and suggest candidate genes for improving meat quality through molecular genetic breeding programs in guinea pigs.