This study was performed to investigate the effects of dietary inclusion of 20% rapeseed meal (RSM) as an alternative to soybean meal (SBM) in a three-month feeding experiment with growing finishing pigs. RNAseq pipeline using Tophat2-Cuffdiff identified 57 upregulated and 63 downregulated genes in RSM compared to SBM pigs. Significantly enriched among downregulated pathways was p53–mediated signaling involved in cellular proliferation, while activation of negative growth regulators (IER5, KLF10, BTG2, KLF11, RETREG1, PRUNE2) in RSM fed pigs provided further evidence for reduced proliferation and increased cellular death, following the observed reduction in performance traits. Upregulation of well-known metabolic controllers (PDK4, UCP3, ESRRG, and ESRRB), involved in energy homeostasis (glucose and lipid metabolism, and mitochondrial function), suggested less available energy and nutrients in RSM pigs. Furthermore, several genes supported more pronounced proteolysis (ABTB1, OTUD1, PADI2, SPP1) and reduced protein synthesis (THBS1, HSF4, AP1S2) in RSM muscle tissue. In parallel, higher levels of NR4A3, PDK4 and FGF21, and a drop in adropin, ELOVL6 and CIDEC/FSP27 indicated increased lipolysis and fatty acid oxidation, reflective of lower dressing percentage. Finally, pigs exposed to RSM showed the greater expression level of genes responsive to oxidative stress, indicated by the upregulation of GPX1, GPX2, and TXNIP.  In general, pigs fed the RSM test diet exhibited reduced growth performance compared to pigs on the SBM control diet. Significant transcriptional changes in the skeletal muscle of growing pigs fed RSM diet was likely the consequence of an increased amount of fiber and higher polyunsaturated fatty acids, and the presence of bioactive phytochemicals, such as glucosinolates.