Comparison of Growth Performance, Immunity, Antioxidant Capacity, and Liver Transcriptome of Calves between Whole Milk and Plant Protein-Based Milk Replacer under the Same Energy and Protein Levels

High-cost milk proteins necessitate cheaper, effective milk replacer alternatives, such as plant proteins. To examine plant protein-based milk replacer’s impact on growth performance, serum immune and antioxidant indicators, and liver transcriptome profiles in suckling calves. We assigned 28 newborn Holstein calves (41.60 ± 3.67 kg of body weight at birth) to milk (M) or milk replacer (MR) and starter diets pre-weaning (0–70 d of age) but with the same starter diet post-weaning (71–98 d of age). During the pre-weaning period, compared with the M group, MR group had significantly lower body weight, withers height, heart girth, average daily gain, feed efficiency, serum immunoglobulin (Ig) M concentration, superoxide dismutase concentration, and total antioxidant capacity; whereas they had significantly higher serum aspartate aminotransferase concentration. During the post-weaning period, MR group presented significantly higher average daily gain, alanine transaminase, aspartate aminotransferase, and malonaldehyde concentrations; whereas they had significantly lower serum IgA and IgM concentrations than the M group. Transcriptome analysis revealed 1, 120 and 293 differentially expressed genes (DEGs; MR vs. M group) in the calves from pre- and post-weaning periods, respectively. The DEGs related to xenobiotic and lipid metabolism and those related to energy metabolism, immune function, and mineral metabolism were up- and downregulated, respectively, during the pre-weaning period; during the post-weaning period, the DEGs related to osteoclast differentiation and metabolic pathways showed difference. In this study, compared with M group, MR group had the same growth performance during the overall experimental period; however, MR affected the hepatic metabolism, immune, and antioxidant function of calves. These observations can facilitate future studies on milk replacers.