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 al dente; drain and set aside.
Chop or tear the spinach, heat the olive oil in a large skillet over medium-low, add the spinach and cook just until wilted, about 3–4 minutes; remove from heat.
In a large mixing bowl, combine the cooked penne, marinara sauce, wilted spinach, and drained artichoke hearts; toss 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.
Spread half of the penne mixture into a 9 x 13-inch casserole dish, top with half of the cheese mixture, then repeat with the remaining penne and cheese so the cheese layer is on top.
Sprinkle the Parmesan evenly over the top and add more freshly ground black pepper if desired.
Bake uncovered until the casserole is hot and bubbly, about 30 minutes; remove from oven and let rest a few minutes before serving.
