It was evaluated whether upper-body compared to lower-body musculature exhibits a different phenotype in relation to capacity for handling reactive oxygen species (ROS), H+, La-, Na+, K+ and also whether it differs in adaptive potential to exercise training. Eighty-three sedentary premenopausal women aged 45 ± 6 years (mean ± SD) were randomized into a high-intensity intermittent swimming group (HIS, n = 21), a moderate-intensity swimming group (MOS, n = 21), a soccer group (SOC, n = 21), or a control group (CON, n = 20). Intervention groups completed three weekly training sessions for 15 weeks, and pre- and postintervention biopsies were obtained from deltoideus and vastus lateralis muscle. Before training, monocarboxylate transporter 4 (MCT4), Na+/K+ pump α2, and superoxide dismutase 2 (SOD2) expressions were lower (P < 0.05) in m deltoideus than in m vastus lateralis, whereas deltoid had higher (P < 0.05) Na+/H+ exchanger 1 (NHE1) expression. As a result of training, Na+/K+ pump α2 isoform expression was elevated only in deltoideus muscle, while upregulation (P < 0.05) of the α1 and β1 subunits, phospholemman (FXYD1), NHE1, and superoxide dismutase 1 expression occurred exclusively in vastus lateralis muscle. The increased (P < 0.05) expression of MCT4 and SOD2 in deltoid muscle after HIS and vastus lateralis muscle after SOC were similar. In conclusion, arm musculature displays lower basal ROS, La-, K+ handling capability but higher Na+-dependent H+ extrusion capacity than leg musculature. Training-induced changes in the ion-transporting and antioxidant proteins clearly differed between muscle groups.