Preheat the oven to 375°F (190°C).
Bring a large pot of salted water to a boil and cook the whole wheat penne until just al dente; drain and set aside.
Chop or tear the spinach into small pieces. Heat the olive oil in a large skillet over medium-low heat, add the spinach and cook until wilted, about 3–4 minutes; remove from heat.
In a large bowl, combine the cooked penne, marinara sauce, wilted spinach, and drained artichoke hearts; toss gently to combine.
In another bowl, mix the cottage cheese, shredded mozzarella, ricotta, egg white, dried oregano, black pepper, crushed red pepper flakes, and salt until evenly combined.
Spoon half of the penne mixture into a 9 x 13-inch casserole dish, spread half of the cheese mixture over it, then repeat with the remaining penne and cheese mixture so the cheese is the top layer.
Sprinkle the grated Parmesan evenly over the top and add additional freshly ground black pepper if desired.
Bake in the preheated oven until hot and bubbly and the top is lightly golden, about 30 minutes; remove and let rest a few minutes before serving.