Updated project metadata. Background: monogastric feeding is dependent on conventional feedstuffs such as corn and soybean meal. However, these are increasingly expensive and environmentally unsustainable. Therefore, there is an increasing interest in high quality and sustainable alternative feedstuffs, namely microalgae. Chlorella vulgaris is one of such alternatives, with a high level of crude protein and bioactive compounds. However, its recalcitrant cell wall hinders the digestive process. CAZyme supplementation is a possible solution to overcome such a problem. The objective of this work was to evaluate the effect of a 5% dietary C. vulgaris (CV) and enzymatic supplementation (CV+R – Rovabio® Excel AP; CV+M – four CAZyme mix) on muscle transcriptome and proteome of finishing pigs in an integrated approach. Results: there were no differences concerning the live pig production performance. Pigs that were fed with the microalga had increased deposition of n-3 PUFA, including C20:5n-3 (EPA) in the muscle. Control pigs increased the abundance of contractile apparatus (e.g. MYH1, MYH2, MYH4) and energy metabolism (e.g. CKMT1, NDUFS3) proteins, demonstrating increased nutrient availability. Moreover, they had increased abundance of SCD, characteristic of increased glucose availability via the activation of SREBP-1c and ChREBP. CV and CV+R pigs upregulated proteolytic and apoptotic genes (e.g. BAX, DDA1), whilst increasing the abundance of glucose (UQCRFS1) and fatty acid catabolism (ACADS) proteins. CV+R pigs upregulated ACOT8 and SIRT3 genes as a response to reduced nutrient availability, to maintain energy homeostasis and oxidative status. The CV+M pigs showed the least number of significant differences in both omics platforms. Conclusions: the four-CAZyme mix designed to degrade the microalgal cell wall was efficient in re-establishing the muscle metabolism, mitigating the otherwise negative effects of microalga incorporation in the diet.